Pyridine → N-(5-bromopyrazin-2-yl)-2,2-dimethylpropanamide

Temperature

0 °C

A solution of 2-amino-5-bromopyrazine (10.00 g, 57.47 mmol) and pyridine (5.6 mL, 68.96 mmol) in methylene chloride (144 mL) was cooled to 0° C. and then was treated slowly with trimethylacetyl chloride (8.6 mL, 68.96 mmol). The resulting reaction mixture was stirred at 0° C. for 30 min and then was allowed to warm to 25° C. where it was stirred for 18 h. At this time, the reaction mixture still contained the starting material 2-amino-5-bromopyrazine. The reaction mixture was treated with an additional amount of trimethylacetyl chloride (4.3 mL, 34.48 mmol) and then stirred at 25° C. for 4 h. The reaction mixture was then concentrated in vacuo to remove methylene chloride. The resulting residue was diluted with ethyl acetate (700 mL). The organic layer was washed with a 1N aqueous hydrochloric acid solution (2×200 mL) and a saturated aqueous sodium chloride solution (1×200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 65M, Silica, 1/9 ethyl acetate/hexanes) afforded N-(5-bromo-pyrazin-2-yl)-2,2-dimethyl-propionamide (12.19 g, 82%) as a white solid: mp 122–124° C.; (ES)+-HRMS m/e calcd for C9H12BrN3O (M+H)+ 258.0237, found 258.0240.

1. customThe resulting reaction mixture
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 18 h
4. stirringstirred at 25° C. for 4 h
5. concentrationThe reaction mixture was then concentrated in vacuo
6. customto remove methylene chloride
7. additionThe resulting residue was diluted with ethyl acetate (700 mL)
8. washThe organic layer was washed with a 1N aqueous hydrochloric acid solution (2×200 mL)
9. dry with materiala saturated aqueous sodium chloride solution (1×200 mL), dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-e818576c669c4a7b9ba8b4c8542a9886

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07132425B2